Kurimoto Makoto, Yoh Tomoaki, Hori Yutaro, Nishino Hiroto, Yoshimura Kohei, Kanda Shuhei, Okura Keisuke, Takamatsu Yuichi, Satoh Motohiko, Nishio Takahiro, Iwaisako Keiko, Ishii Takamichi, Hatano Etsuro
Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Kyoto, Sakyo-Ku, 606-8507, Japan.
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Sci Rep. 2025 Aug 25;15(1):31229. doi: 10.1038/s41598-025-15310-3.
Intrahepatic cholangiocarcinoma (ICC) is a rare but highly malignant liver cancer. Surgical resection provides the best long-term survival, yet poor prognosis requires improved treatments. Galectin-9 (GAL9) has gained attention for its role in tumor biology. This study investigated circulating galectin-9 (cGAL9) levels in ICC patients undergoing resection, along with tumor tissue characteristics.
GAL9 expression levels in circulating and tumor cells were measured using enzyme-linked immunosorbent assay and immunohistochemistry (IHC) in 91 ICC surgical patients. The mRNA expression levels of candidate genes were analyzed in 44 available frozen tissue samples.
The optimal cGAL9 cutoff was 12.0 ng/ml using minimum P value approach. Higher cGAL9 levels linked to multiple tumors (P = 0.046), poorer overall survival (OS), and recurrence-free survival (RFS). Tumor cell GAL9 expression by IHC did not correlate with OS or RFS. cGAL9 levels did not correlate with tumor cell expression in IHC analyses or GAL9 mRNA in resected specimens. However, cGAL9 levels correlated with mRNA levels of glycolysis markers (glucose transporter 1 and hypoxia inducible factor 1 alpha).
Preoperative cGAL9 serves as a novel prognosticator for ICC patients after surgical resection. Its association with glycolysis highlights the potential for therapeutic guidance.
肝内胆管癌（ICC）是一种罕见但恶性程度很高的肝癌。手术切除可提供最佳的长期生存率，但预后较差需要改进治疗方法。半乳糖凝集素-9（GAL9）因其在肿瘤生物学中的作用而受到关注。本研究调查了接受手术切除的ICC患者的循环半乳糖凝集素-9（cGAL9）水平以及肿瘤组织特征。
采用酶联免疫吸附测定法和免疫组织化学（IHC）检测91例接受ICC手术患者的循环和肿瘤细胞中的GAL9表达水平。对44份可用的冷冻组织样本分析候选基因的mRNA表达水平。
采用最小P值法确定的cGAL9最佳临界值为12.0 ng/ml。较高的cGAL9水平与多发肿瘤（P = 0.046）、较差的总生存期（OS）和无复发生存期（RFS）相关。通过IHC检测的肿瘤细胞GAL9表达与OS或RFS无关。在IHC分析中，cGAL9水平与肿瘤细胞表达或切除标本中的GAL9 mRNA均无相关性。然而，cGAL9水平与糖酵解标志物（葡萄糖转运蛋白1和缺氧诱导因子1α）的mRNA水平相关。
术前cGAL9可作为ICC患者手术切除后的一种新的预后指标。其与糖酵解的关联突出了其在治疗指导方面的潜力。
